The invention is directed to implantable brachytherapy devices.
It is known to treat proliferative tissue, such as tumors, lesions and stenoses of biological passageways, with radiation in order to inhibit or prevent cellular proliferation by preventing replication and migration of cells and by inducing programmed cell death. Traditional high-dose external beam radiation treatment, and prolonged low dose rate, close-distance radiation treatment (brachytherapy), are well-established therapies for the treatment of cancer, a malignant form of cellular proliferation.
It is important in the administration of radiation that it be properly targeted so as to be effective against undesirable cellular proliferation without adversely affecting normal cellular responses. Externally applied radiation requires careful control over the depth and breadth of radiation penetration so as not to damage healthy tissue surrounding the lesion to be treated. Close-distance radiation treatment also requires careful control over the penetration and directionality of the radiation, but this can be done over substantially smaller distances.
The radioactivity may be incorporated into or onto an implantable device. Such implantable devices are typically quite expensive to manufacture. In particular, if radioactivity is added to the device, the device may only be effective for brachytherapy during a relatively short period during which the radioactivity is provided at a useful (therapeutic) level. Depending on the radioisotope used, the decay time may be as short as hours, days or weeks.
The current state of the art brachytherapy for treatment of localized lesions such as tumors of, for example, the prostate, breast, brain, eye, liver, or spleen, employs radioactive, sealed source seeds. The term xe2x80x9csealed sourcexe2x80x9d, as used herein, means that radioisotopes incorporated into a device are integral with the device and cannot be dislodged or released from the host material of the device in the environment of usage. A typical sealed source seed includes a radiation source encapsulated within an impermeable, biocompatible capsule made of, for example, titanium, which is designed to prevent any leaching or release of the radioisotope. The seeds are approximately the size of a grain of rice (typically 0.81 mm in diameter by 4.5 mm long) and are implanted individually at a treatment site within and/or around a lesion, typically with a medium bore (18-gauge) delivery needle.
Disadvantages of the use of such seeds as brachytherapy devices include their nature as discrete, or point, sources of radiation, and the corresponding discrete nature of the dosages which they provide. In order to provide an effective radiation dose over an elongated or wide target area, the seeds should be uniformly and relatively closely spaced. The need to ensure accurate and precise placement of numerous individual radiation sources undesirably prolongs the surgical procedure, and hence the exposure of the surgical team to radiation. Moreover, the use of discrete seeds requires an elaborate grid matrix for their proper placement. This requirement is labor-intensive, and therefore costly. In addition, the discrete nature of the seeds renders them more susceptible to migration from their intended locations, thereby subjecting portions of the lesion, the treatment site, and surrounding healthy tissue to over- or under-dosage, reducing the effectiveness and reliability of the therapy.
Other disadvantages exist in radioactive seed therapy. Relatively few radionuclides are suitable for use in sealed-source seeds, because of limited availability of radioisotopes with the necessary combination of half-life, specific activity, penetration depth and activity, and geometry. In addition, the implantation of seeds generally requires a delivery needle with a sufficiently large bore to accommodate the seeds and may, in some cases, require an additional tubular delivery device. The use of a relatively large delivery needle during seeding may cause unnecessary trauma to the patient and displacement of the lesion during the procedure. Also, because of the risk of migration or dislodgement of the seeds, there is the risk that healthy tissues near or remote from the lesion site will be exposed to radiation from seeds which have become dislodged from their intended locations and possibly carried from the body within urine or other fluids.
Various radioisotopes have been proposed for brachytherapy. Brachytherapy devices made of palladium-103 are desirable because palladium-103 has a half life of about 17 days and a photon energy of 20.1-23 KeV, which makes it particularly suitable for use in the treatment of localized lesions of the breast, prostate, liver, spleen, lung and other organs and tissues.
Because palladium-103 is unstable and not naturally occurring in the environment, it must be manufactured, generally either by neutron activation of a palladium-102 target, or by proton activation of a rhodium target. These processes are disclosed in, for example, U.S. Pat. No. 4,702,228 to Russell, Jr. et al. (neutron activation) and U.S. Pat. No. 5,405,309 to Carden, Jr. (proton activation).
Brachytherapy devices employing radioisotope coatings are also known. U.S. Pat. No. 5,342,283 to Good discloses the formation of concentric radioactive and other discrete coatings on a substrate by various deposition processes, including ion plating and sputter deposition processes, as well as via exposure of an isotope precursor, such as palladium-102, to neutron flux in a nuclear reactor.
A disadvantage of the radioactive devices made by any of the above processes is that they cannot be made economically or simply. The processes are either prohibitively expensive and require lengthy and costly wet chemistry separation steps to isolate the radioactive isotope from the non-radioactive precursor, or they are relatively complicated, multistep processes which are difficult to control and which may produce coatings that can deteriorate with time and/or exposure to bodily fluids, resulting in dissemination of radioactive and other materials into the body, with potentially harmful consequences.
A highly versatile form of a device for interstitial radiation treatment is a wire or rod which can be inserted into the tissue at a lesion site and then bent or shaped as needed to encircle or otherwise assume a useful shape for administration of radiation to the lesion and/or to surrounding tissue. Greater versatility, flexibility and specificity of treatment can be provided as the size (diameter) of the wire decreases; however, such fine wires are also generally difficult to see, handle and maneuver, and this limits their utility in many treatment applications.
U.S. Pat. No. 5,498,227 to Mawad discloses a shielded implantable radioactive wire which includes a radioactive inner core and a buffer or shielding layer in the form of a flexible metal wire or ribbon wrapped around the core. The purpose of the buffer layer is to attenuate radiation emitted from the inner core. The wire can be formed into a helical coil shape and can be made of a shape-memory material which allows the device to be inserted into a treatment site in a straightened configuration and then relaxed to its original helical shape. The device has particular application as an expandable helical coil stent to deliver therapeutic radiation to, and maintain the patency of, occluded biological passageways. The diameter of the inner core, as well as of the wire used as the buffer layer, is in the range of about ten to fifty thousandths of an inch (0.010xe2x80x3-0.050xe2x80x3), or about 0.25 to 1.25 millimeter, and the diameter of the helical coil formed from the wire is in the range of about 1 millimeter to 2 centimeters.
U.S. Pat. Nos. 5,176,617 and 5,722,984 to Fischell et al. also disclose radioactive helical coil stents for use in maintaining the patency of biological passageways. Such stents generally have an undeployed diameter in the range of about 1.5 to 2 millimeters, and a deployed diameter in the range of about 2 to 4 millimeters.
A problem with the Mawad and Fischell et al. devices is that they are generally characterized by a stiffness and rigidity which, although beneficial in maintaining the patency of a lumen or passageway, are not optimum for use in many applications in which extra-luminal brachytherapy, such as, for example, interstitial brachytherapy, is needed.
It would therefore be an advancement in the art to provide a highly versatile, highly flexible, general purpose brachytherapy device for use primarily in interstitial applications which can also be relatively easily and economically fabricated.
According to one aspect of the invention, there is provided an implantable brachytherapy device comprising a radioactive coiled wire. The diameter of the wire for almost all applications is between about 10 and about 200 micrometers, and the outer diameter of the coil is between about 25 and about 1000 micrometers (1 millimeter). In this range the wire is very thin and may be difficult to handle and see with the naked eye and, when in the body, difficult to detect using x-ray and ultrasound imaging techniques. By coiling the wire the device is easier to handle and to see, both with the naked eye and when in the body under x-ray or ultrasound. Further, in one application, the brachytherapy device is sufficiently adaptable so that when it is positioned in proximity to a lesion, the device can shrink and/or change it shape as the lesion shrinks and/or changes shape. The device is thus highly useful in interstitial brachytherapy applications.
The radioactive coiled wire preferably includes one or more radioisotopes which have been incorporated into the wire so that the wire comprises a substantially unitary material. The term xe2x80x9csubstantially unitary materialxe2x80x9d, as used herein, refers to a radioisotope-containing material which retains virtually all of the properties (mechanical, chemical, electrical, optical, etc.) of the host material prior to incorporation of the radioisotope. More specifically, when a substantially unitary material includes a radioisotope, there is no distinguishable interface between the host material and the radioisotope.
In one preferred embodiment, the wire is made substantially of a transmutable material which can be converted to a radioactive material upon exposure of the wire to an accelerated beam of charged particles having a predetermined energy. The charged particles can be protons, deuterons or alpha particles. In one preferred embodiment, the transmutable material comprises rhodium and the radioactive material comprises palladium-103. In another preferred embodiment, the transmutable material comprises tantalum and the radioactive material comprises tungsten-181. In other embodiments, the transmutable material can comprise, for example, stainless steel, which includes iron, carbon and various alloying agents such as chromium, cobalt, vanadium, titanium, tantalum, tungsten, and nickel, and minor amounts of other elements such as manganese and arsenic. The radioactive material will comprise one or more of various radioisotopes of these alloying elements.
According to another embodiment, ion implantation techniques can be used to incorporate the radioisotope into the wire so that the wire comprises a substantially unitary material.
According to still another embodiment, the wire includes one or more radioisotopes which have been applied onto the wire as a thin film so that the wire comprises a substantially xe2x80x9cnear-unitaryxe2x80x9d material. A xe2x80x9cnear-unitaryxe2x80x9d material, as the term is used herein, is defined as a material which retains substantially all of the mechanical properties of the wire, or host material, prior to application of the radioisotope. The radioisotope is applied as a thin film onto the wire and is not integrated into the material of the wire.
The device of the invention is preferably adapted for either substantially permanent or temporary implantation into a patient and may include anchoring structures at points along its length or at its ends for securing the device in tissue.
The intensity of the radioactivity of the wire, prior to its formation into a coil, is a function of the location and type of radioisotope(s) in or on it. The intensity of the radioactivity of the coil is a function of not only these parameters, but also of the shape, size, turns density and pitch angle of the coil. The coiled wire preferably has an aspect ratio (ratio of coil length to coil diameter) of at least 3 to 1. The pitch angle can vary from essentially zero degrees, so that the wire is essentially linear, to ninety degrees, so that the coil is so tightly wound that it essentially defines a tubular structure.
In a preferred embodiment, the diameter of the wire is about 50 micrometers and the outer diameter of the coil formed from the wire is about 350 micrometers.
According to another aspect of the invention, there is provided a method of making an implantable coiled brachytherapy device. The method comprises the steps of providing a flexible wire of a non-radioactive material, incorporating one or more radioisotopes into at least a portion of the wire so that the wire comprises a substantially unitary material, and forming the wire into a coil having a preselected shape, size, turns density, pitch angle and sufficient flexibility such that the coil can change shape in response to changes in surrounding tissue. Such changes could include, for example, changes in the shape, size, location and/or contour of the lesion and/or the surrounding tissue.
In an alternate embodiment, the method comprises the steps of providing a flexible wire of a non-radioactive material, forming the wire into a coil having a preselected shape, size, turns density, pitch angle, and sufficient flexibility such that the coil can change shape in response to changes in surrounding tissue, and incorporating one or more radioisotopes into at least a portion of the wire so that the wire comprises a substantially unitary material.
In a preferred embodiment, the wire or coil can be made radioactive by nuclear transformation or ion implantation techniques so as to create a substantially unitary material.
According to another aspect of the invention, there is provided a method of making an implantable coiled brachytherapy device. The method comprises the steps of providing a flexible wire of a non-radioactive material, applying a thin film containing one or more radioisotopes onto at least a portion of the wire so that the wire comprises a substantially near-unitary material, and forming the wire into a coil having a preselected shape, size, turns density and pitch angle.
In an alternate embodiment, the method comprises the steps of providing a flexible wire of a non-radioactive material, forming the wire into a coil having a preselected shape, size, turns density and pitch angle, and applying a thin film containing one or more radioisotopes onto at least a portion of the wire so that the wire comprises a substantially near-unitary material.
In a preferred embodiment, the total thickness of the film is not greater than about 1 percent of the outer diameter of the coil.
According to still another aspect of the invention, there is provided a method of making an implantable coiled brachytherapy device. The method comprises the steps of providing a flexible wire of a non-radioactive material having a diameter of between about 10 and about 200 micrometers, incorporating one or more radioisotopes into at least a portion of the wire so that the wire comprises a substantially unitary material, and forming the wire into a coil having an outer diameter of between about 25 and about 1000 micrometers and having a preselected shape, turns density and pitch angle.
In an alternate embodiment, the method comprises the steps of providing a flexible wire of a non-radioactive material having a diameter of between about 10 and about 200 micrometers, forming the wire into a coil having an outer diameter of between about 25 and about 1000 micrometers and having a preselected shape, turns density and pitch angle, and incorporating one or more radioisotopes into at least a portion of the wire so that the wire comprises a substantially unitary material.
According to still another aspect of the invention, a method of making an implantable coiled brachytherapy device comprises the steps of providing a flexible wire of a non-radioactive material having a diameter of between about 10 and about 200 micrometers, applying a thin film containing one or more radioisotopes onto at least a portion of the wire so that the wire comprises a substantially near-unitary material, and forming the wire into a coil having an outer diameter of between about 25 and about 1000 micrometers and having a preselected shape, turns density and pitch angle.
In an alternate embodiment, the method comprises the steps of providing a flexible wire of a non-radioactive material having a diameter of between about 10 and about 200 micrometers, forming the wire into a coil having an outer diameter of between about 25 and about 1000 micrometers and having a preselected shape, turns density and pitch angle, and applying a thin film containing one or more radioisotopes onto at least a portion of the wire so that the wire comprises a substantially near-unitary material.
These and other objects and advantages of the invention will in part be obvious and will in part appear hereinafter. The invention accordingly comprises the apparatus possessing the construction, combination of elements and arrangement of parts which are exemplified in the following detailed disclosure, the scope of which will be indicated in the claims.